This invention relates to a system for sensing ionic components. More particularly, the invention relates to compositions, apparatus and methods useful for sensing ionic components, e.g., hydrogen or hydroxyl ions-measured by pH, in fluids, such as blood.
It is often advantageous to determine the concentration of an ionic component in a given fluid. For example, medical diagnostic and/or treatment procedures may involve the determination of the pH value of a patient's blood or other bodily fluid. Such determinations may be made very frequently, even continuously, during treatment.
One problem which has arisen is that any one ionic component indicator, e.g., pH indicator, is effective over only its "effective indicator range", i.e., a limited range of concentrations of the ionic component, e.g., a limited pH range, where reliable determinations can be obtained using the given indicator. For example, each pH indicator has a unique pKa associated with a unique pH response range. Therefore, each pH indicator is useful over a limited pH range, e.g., of about one pH unit. Thus, if the concentration of the ionic component in a given medium is outside the "effective indicator range", reliable concentration determinations cannot be obtained without changing the indicator. A pH indicator, e.g., dye, with an appropriate pKa is needed for each pH range of interest. A different indicator, e.g., dye, with a different pKa is needed outside this range. It would be advantageous to use an indicator outside its "effective indicator range". For example, in the medical area, it may be useful to employ an indicator in the physiological range even though its normal "effective indicator range" is located outside this range.
Indicators are often used in combination with matrix materials, such as polymeric materials. For example, Seitz et al U.S. Pat. No. 4,548,907 teaches the use of a pH sensitive fluorophor (8-hydroxy-1,3,6-pyrenetrisulfonic acid) which is electrostatically bound to an ion exchange membrane, such as an anion exchanger. Seitz et al uses the ion exchange membrane to immobilize the fluorophor to measure physiological pH's by a ratioing technique.
Edwards U.S. Pat. No. 3,449,080 teaches a device for measuring the level of electrolyte in body fluid for diagnostic purposes which comprises a carrier containing a polymeric material having ion exchange characteristics which is capable of exchanging ions with the electrolyte whose level is to be measured, and a material which is color responsive to the extent of the ion exchange. In effect, the species the color of which the material is color responsive to is the product of the ion exchange. Wang U.S. Pat. No. 4,473,650 also discloses a system in which an ion exchange product is used to measure a characteristic of a test sample.
Sommer et al U.S. Pat. No. 4,543,335 discloses a method for preparing a device for the quantitative determination of heparin in mammalian blood plasma which involves coating a carrier matrix with a fluorogenic or chromogenic substrate solution. Buffer is included in two layers of the device because the rate of thrombin enzymatic reaction is pH dependent. The pH of the buffer in both layers is designed to maximize the reaction of thrombin and the substrate.
Harper U.S. Pat. No. 3,904,373 teaches bound pH indicators which include any complex comprising an organic species covalently coupled via a silane coupling agent to a carrier, preferably an inorganic carrier having available hydroxyl or oxide groups. Such inorganic carriers include glass silica gel, colloidal silica, woilastonite, and bentonite. Harper does not teach carriers which are anionic or cationic after the coupling. Further, Harper lists a large number of pH indicators, thus impliedly suggesting that each indicator is to be used for a different pH range. Harper does not teach extending the effective range of any pH indicator.
For biological fluids, a prior known sensor uses the fluorescent properties of a dye in conjunction with the ionic permeability of a preformed integral cellulose membrane sheet. In this sensor, the cellulose membrane is chemically treated so as to introduce covalent bondable groups onto the membrane. The dye is then covalently bonded to these groups to adhere the dye to the membrane. Substantially all the covalently bondable groups introduced onto the membrane are used to covalently bond the dye to the membrane. Thus, the dye is adhered to a substantially nonionic matrix material. A small disk is cut from the membrane sheet and is attached to a cassette in association with an optical fiber bundle also attached to the cassette. When the dye is excited by excitation light imposed on the dye along the fibers, it undergoes fluorescence, emitting a wavelength of light at a different wavelength than the excitation wavelength. The emission light is measured as an indication of the pH.